Schisandrin B regulates lipid metabolism in subcutaneous adipocytes

Hiu Yee Kwan,Anfernee Kai Wing Tse,Wang Fun Fong,Bin Liu,Zhi-Ling Yu,Jiahui Wu,Xiuqiong Fu,Xiao-Juan Chao,Chi Leung Chan,Tao Su,Hua Yu

doi:10.1038/s41598-017-10385-z

Abstract

Subcutaneous adipocytes in obese subjects have a lower sensitivity to catecholamine-induced lipolysis and a higher sensitivity to insulin anti-lipolytic effects compared to adipocytes in other adipose depots. Therefore, increasing lipolysis in subcutaneous adipocytes coupled with enhanced fatty acid oxidation may be an anti-obesity strategy. Schisandrin B (Sch B) is one of the most abundant active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis which is a commonly prescribed Chinese medicinal herb. We found that Sch B reduced glycerolipid contents in 3T3-L1 adipocytes and subcutaneous adipocytes dissected from DIO mice. Sch B also activated hormone sensitive lipase (HSL) and increased lipolysis in these adipocyte in a protein kinase A-dependent manner. Interestingly, Sch B increased fatty acid oxidation gene expressions in these adipocytes, implying an increase in fatty acid oxidation after treatment. In in vivo model, we found that Sch B increased HSL phosphorylation, reduced glycerolipid levels and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes in the DIO mice. More importantly, Sch B significantly reduced the subcutaneous adipocyte sizes, subcutaneous adipose tissue mass and body weight of the mice. Our study provides scientific evidence to suggest a potential therapeutic function of Sch B or Schisandra chinensis seed containing Sch B in reducing obesity.

Highlights

The incidence of obesity has been increasing over the past decades[1]
We found that Schisandrin B (Sch B) significantly increased hormone sensitive lipase (HSL) phosphorylation (Fig. 8a,b and Fig. S3), reduced glycerolipid levels (Fig. 8c) and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes (Fig. 8d), suggesting Sch B regulates the lipid metabolism in the subcutaneous adipocytes in vivo
We showed that Sch B regulated adipocyte lipid metabolism

Summary

Introduction

The incidence of obesity has been increasing over the past decades[1]. According to World Health Organization, obesity and overweight are linked to more deaths than underweight worldwide. Many mouse models showed that increased lipolysis and fatty acid oxidation within adipocytes reduced body weight. A study showed that adipose-tissue-specific adipocyte triglyceride lipase (ATGL) overexpressing mice were leaner, with smaller adipocyte sizes and decreased TG contents in adipose tissues compared to control mice[15] Another animal model showed that adipose-specific targeting of the pseudokinase Tribbles 3 resulted in enhanced lipolysis and fatty acid oxidation, which protected the mice from diet-induced obesity[16]. Example of transgenic mice with enhanced adipocyte fatty acid oxidation resulted in leanness[17] All these studies suggest that regulating adipocyte lipid metabolism, increasing lipolysis coupled with enhanced fatty acid oxidation within adipocytes is a promising strategy to reduce obesity. We examined the functional role of Sch B in reducing subcutaneous adipose tissue mass by regulating the adipocyte lipid metabolism

Methods

Results

Conclusion